Antioxidant Effect of Barley Sprout Extract via Enhancement of Nuclear Factor-Erythroid 2 Related Factor 2 Activity and Glutathione Synthesis.

Yun-Hee Lee,Woo-Duck Seo,Kyung-Mi Kim,Sung Ki,Young-Suk Jung,Jin Hong,Jae-Hwan Kwak,Tae Son,Jae-Chul Jung,Seunghyun Lee,Sou Kim

doi:10.3390/nu9111252

Abstract

We previously showed that barley sprout extract (BSE) prevents chronic alcohol intake-induced liver injury in mice. BSE notably inhibited glutathione (GSH) depletion and increased inflammatory responses, revealing its mechanism of preventing alcohol-induced liver injury. In the present study we investigated whether the antioxidant effect of BSE involves enhancing nuclear factor-erythroid 2 related factor 2 (Nrf2) activity and GSH synthesis to inhibit alcohol-induced oxidative liver injury. Mice fed alcohol for four weeks exhibited significantly increased oxidative stress, evidenced by increased malondialdehyde (MDA) level and 4-hydroxynonenal (4-HNE) immunostaining in the liver, whereas treatment with BSE (100 mg/kg) prevented these effects. Similarly, exposure to BSE (0.1–1 mg/mL) significantly reduced oxidative cell death induced by t-butyl hydroperoxide (t-BHP, 300 μM) and stabilized the mitochondrial membrane potential (∆ψ). BSE dose-dependently increased the activity of Nrf2, a potential transcriptional regulator of antioxidant genes, in HepG2 cells. Therefore, increased expression of its target genes, heme oxygenase-1 (HO-1), NADPH quinone oxidoreductase 1 (NQO1), and glutamate-cysteine ligase catalytic subunit (GCLC) was observed. Since GCLC is involved in the rate-limiting step of GSH synthesis, BSE increased the GSH level and decreased both cysteine dioxygenase (CDO) expression and taurine level. Because cysteine is a substrate for both taurine and GSH synthesis, a decrease in CDO expression would further contribute to increased cysteine availability for GSH synthesis. In conclusion, BSE protected the liver cells from oxidative stress by activating Nrf2 and increasing GSH synthesis.

Highlights

Chronic alcohol consumption results in alcoholic liver disease (ALD) that encompasses a spectrum of injury, ranging from fatty liver disease to irreversible cirrhosis [1]
Cytochrome P450 2E1 (CYP2E1) in the hepatocytes is mainly responsible for the metabolism of ethanol and these toxic metabolites induce NADPH oxidase activity in the Kupffer cells, abnormal mitochondrial function, disturbance in lipid metabolism, and cytokine production [4,5,6]
We previously demonstrated that barley sprout extract (BSE) prevents liver injury induced by chronic alcohol intake in mice by suppressing inflammatory responses and preventing GSH depletion [23]

Summary

Introduction

Chronic alcohol consumption results in alcoholic liver disease (ALD) that encompasses a spectrum of injury, ranging from fatty liver disease to irreversible cirrhosis [1]. Alcohol induces oxidative stress by free radical formation, which mainly contributes to liver injury [3]. Ethanol is oxidized to toxic metabolite, acetaldehyde. Cytochrome P450 2E1 (CYP2E1) in the hepatocytes is mainly responsible for the metabolism of ethanol and these toxic metabolites induce NADPH oxidase activity in the Kupffer cells (liver-resident macrophages), abnormal mitochondrial function, disturbance in lipid metabolism, and cytokine production [4,5,6]. Chronic alcohol consumption induces hepatic CYP2E1, which accelerates oxidation of ethanol to acetaldehyde, and generates reactive oxygen species (ROS) [7]. Deletion of CYP2E1 protects mice from chronic alcohol consumption-induced liver injury via reduction of ROS [8]

Methods

Results

Conclusion